Endogenous Stem Cells Research Articles

HMGB1-Mediated Activation of the Inflammatory-Reparative Response Following Myocardial Infarction.

Different cell types belonging to the innate and adaptive immune system play mutually non-exclusive roles during the different phases of the inflammatory-reparative response that occurs following myocardial infarction. A timely and finely regulation of their action is fundamental for the process to properly proceed. The high-mobility group box 1 (HMGB1), a highly conserved nuclear protein that in the extracellular space can act as a damage-associated molecular pattern (DAMP) involved in a large variety of different processes, such as inflammation, migration, invasion, proliferation, differentiation, and tissue regeneration, has recently emerged as a possible regulator of the activity of different immune cell types in the distinct phases of the inflammatory reparative process. Moreover, by activating endogenous stem cells, inducing endothelial cells, and by modulating cardiac fibroblast activity, HMGB1 could represent a master regulator of the inflammatory and reparative responses following MI. In this review, we will provide an overview of cellular effectors involved in these processes and how HMGB1 intervenes in regulating each of them. Moreover, we will summarize HMGB1 roles in regulating other cell types that are involved in the different phases of the inflammatory-reparative response, discussing how its redox status could affect its activity.

Hydrogel composite scaffolds achieve recruitment and chondrogenesis in cartilage tissue engineering applications

BackgroundThe regeneration and repair of articular cartilage remains a major challenge for clinicians and scientists due to the poor intrinsic healing of this tissue. Since cartilage injuries are often clinically irregular, tissue-engineered scaffolds that can be easily molded to fill cartilage defects of any shape that fit tightly into the host cartilage are needed.MethodIn this study, bone marrow mesenchymal stem cell (BMSC) affinity peptide sequence PFSSTKT (PFS)-modified chondrocyte extracellular matrix (ECM) particles combined with GelMA hydrogel were constructed.ResultsIn vitro experiments showed that the pore size and porosity of the solid-supported composite scaffolds were appropriate and that the scaffolds provided a three-dimensional microenvironment supporting cell adhesion, proliferation and chondrogenic differentiation. In vitro experiments also showed that GelMA/ECM-PFS could regulate the migration of rabbit BMSCs. Two weeks after implantation in vivo, the GelMA/ECM-PFS functional scaffold system promoted the recruitment of endogenous mesenchymal stem cells from the defect site. GelMA/ECM-PFS achieved successful hyaline cartilage repair in rabbits in vivo, while the control treatment mostly resulted in fibrous tissue repair.ConclusionThis combination of endogenous cell recruitment and chondrogenesis is an ideal strategy for repairing irregular cartilage defects.Graphical

Rosiglitazone Ameliorates Spinal Cord Injury via Inhibiting Mitophagy and Inflammation of Neural Stem Cells.

Background Neurodegenerative diseases, such as Alzheimer's disease, and traumatic brain and spinal cord injury (SCI) are prevalent in clinical practice. Inhibition of hyperactive inflammation and proliferation of endogenous neural stem cells (NSCs) is a promising treatment strategy for SCI. Our previous studies demonstrated the beneficial effects of rosiglitazone (Rosi) on SCI, but its roles in inflammation inhibition and proliferation of NSCs are unknown. Methods SCI in a rat model was established, and the effects of Rosi on motor functions were assessed. The effects of Rosi on NSC proliferation and the underlying mechanisms were explored in details. Results We showed that Rosi ameliorated impairment of moto functions in SCI rats, inhibited inflammation, and promoted proliferation of NSCs in vivo. Rosi increased ATP production through enhancing glycolysis but not oxidative phosphorylation. Rosi reduced mitophagy by downregulating PTEN-induced putative kinase 1 (PINK1) transcription to promote NSC proliferation, which was effectively reversed by an overexpression of PINK1 in vitro. Through KEGG analysis and experimental validations, we discovered that Rosi reduced the expression of forkhead box protein O1 (FOXO1) which was a critical transcription factor of PINK1. Three FOXO1 consensus sequences (FCSs) were found in the first intron of the PINK1 gene, which could be potentially binding to FOXO1. The proximal FCS (chr 5: 156680169–156680185) from the translation start site exerted a more significant influence on PINK1 transcription than the other two FCSs. The overexpression of FOXO1 entirely relieved the inhibition of PINK1 transcription in the presence of Rosi. Conclusions Besides inflammation inhibition, Rosi suppressed mitophagy by reducing FOXO1 to decrease the transcription of PINK1, which played a pivotal role in accelerating the NSC proliferation.

Isolation and Expansion of Primary Conjunctival Stem Cells (CjSCs) from Human and Rabbit Tissues.

Conjunctival disorders are multivariate degenerative ocular surface diseases that can jeopardize ocular function and impair visual capacity in severe cases. The recent development of stem cell technologies has shed a new light on the treatment of conjunctival disorders as the regenerative medicine using endogenous stem cells becomes a potential therapeutic strategy. However, the efficient in vitro expansion of the endogenous stem cells dominating the conjunctival regeneration, the conjunctival stem cells (CjSCs), remains challenging. Existing protocols largely adopted primary culture using feeder layers, which has limited efficiency and risk of contamination. Here, we report a protocol for the isolation and expansion of primary CjSCs derived from human or animal tissues. This protocol adopts collagenase-based enzymatic digestion to release the primary cells from conjunctival tissues and utilizes a feeder-free culture strategy based on a small molecule inhibitor cocktail that stimulates the expansion of CjSCs. The CjSCs generated with this method were rapidly dividing and highly homogeneous. They also expressed characteristic stem cell markers and exhibited differentiation potency. These findings marked an important step forward in building stable CjSCs in vitro expansion, which will help researchers better understand the biology of ocular surface stem cells and develop innovative regenerative medicine approaches for ocular surface diseases. This protocol was validated in: Biomaterials (2021), DOI: 10.1016/j.biomaterials.2020.120462 Graphical abstract.

Treatment of inflammatory bone loss in periodontitis by stem cell-derived exosomes

Periodontitis is the primary cause of tooth loss, but there is no effective treatment to repair inflammatory bone loss in periodontitis. Exosomes emerge as essential paracrine factors of mesenchymal stem cells (MSCs) that mediated tissue regeneration. Here, we investigated the potential of exosomes secreted by periodontal ligament stem cells (PDLSCs) as therapeutics for the bone defect in periodontitis. Exosomes secreted from PDLSCs derived from healthy periodontal ligaments (h-PDLSCs) and their function were evaluated on PDLSCs isolated from the inflammatory periodontal ligament of periodontitis patients (i-PDLSCs). Treatment of exosomes of h-PDLSCs led to an increase in the formation of mineralized nodules and the expressions of osteogenic genes and proteins in i-PDLSCs. Mechanistically, h-PDLSCs-exosomes suppressed the over-activation of canonical Wnt signaling to recover the osteogenic differentiation capacity of i-PDLSCs. To evaluate the therapeutic of exosomes on inflammatory bone loss, h-PDLSCs-exosomes loaded with Matrigel or β-TCP were employed to repair bone defects in rat models of periodontitis. Compared to the vehicle-treated control group, h-PDLSCs-exosomes-treated rats resulted in more bone formation in the defect of alveolar bone. In conclusion, these results demonstrated that exosomes derived from healthy PDLSCs could rescue the osteogenesis capacity of endogenous stem cells under an inflammatory environment and promote regeneration of alveolar bone. Our findings suggest that MSCs-derived exosome is an effective and practical cell-free MSC therapeutic for the treatment of periodontitis. Statement of significanceThere is no effective treatment to repair inflammatory bone loss in periodontitis. As essential paracrine factors of PDLSCs, exosomes might mediate tissue regeneration during stem cell therapy. Here, we reported that exosomes secreted from healthy PDLSCs promoted the osteogenic differentiation of PDLSCs derived from periodontitis tissue. Healthy PDLSCs-exosomes treatment resulted in accelerated bone formation in the defect of alveolar bone in rat models of periodontitis. Mechanistically, h-PDLSCs-exosomes suppressed the over-activation of canonical Wnt signaling to recover the osteogenic differentiation capacity of inflammatory PDLSCs. These findings suggest that MSCs-derived exosome is an effective and practical cell-free MSC therapeutic for the treatment of periodontitis.

Multifunctional silicon calcium phosphate composite scaffolds promote stem cell recruitment and bone regeneration.

A scaffold is one of the most significant implants for treating bone injury, while the precise control of stem cell proliferation and differentiation within a scaffold is still challenging. In this work, a composite scaffold was designed to be capable of recruiting endogenous stem cells, stimulating osteogenic differentiation and achieving significant bone repair function. The designed SiCP + SF@PFS silica-calcium phosphate composite scaffold was obtained by mixing the peptide PFS containing silk fibroin solution with the SiCP scaffold, and treating with horseradish peroxidase and H2O2. The results showed that the composite scaffold was able to release the PFS peptide continuously to induce the migration of mesenchymal stem cells. Meanwhile, cell proliferation and osteogenic differentiation were also improved after being seeded on the scaffold. In the cranial defect rat model, the composite scaffold was able to recruit CD29+ and CD90+ cells one week after implantation around the injury sites. The results of Micro-CT, H&E staining, Masson's staining and immunohistochemical staining indicated that the composite scaffold was able to promote new bone formation significantly.

Safety and Efficacy of Repeat Doses of Allogeneic Mesenchymal Stem Cells in Patients with Age Related Frailty

Cognitive decline and impairment among older adults have become an important public health issue. Previous research shows older women have a greater prevalence of Alzheimer's disease than Men. Among women, breast cancer is one of the most common types of cancer. Over half of breast cancer deaths occur in women aged 65 and older. Therefore, early detection of breast cancer through mammogram screening is important among older women. This study aimed to examine the influence of cognitive function on adherence to mammogram breast cancer screening among older American women aged 65 and older. Data from the Health and Retirement Study (2012-2016) was obtained and analyzed. The independent variable of the study was cognitive function (normal, not normal). Adherence to mammogram (low, moderate, high) was the dependent variable. Multinomial regression was performed to examine the association between cognitive function and adherence to mammogram after controlling for demographic covariates. In the study, 33.3% of respondents had impaired cognitive function and 21.7% showed low adherence to mammogram screening. Regression results found that older women with impaired cognitive function were more likely to be in low adherence group (OR=1.30, p=0.01) or moderate adherence group (OR=1.47, p<0.001) relatively to be in high adherence group compared to older women with normal cognitive function. The development and implementation of interventions are needed for reducing barriers to accessing cancer screening services in high-risk vulnerable populations. This submission is considered late-breaking research because study findings were obtained from a recently completed student's master's project.

A Phase 2b Clinical Trial Assessing Lomecel-B Infusion in Individuals with Aging Frailty: Study Design and Rationale

Frailty is a common and important geriatric syndrome characterized by age-associated declines in physiology and function across multiple organ systems, which lead to increased vulnerability to adverse health outcomes. A biological mechanism that underlies the decline in physical function associated with aging frailty is chronic inflammation. The MSCs in Lomecel-B have immuno-modulatory capacity and control inflammation and the cytokine production of lymphocytes. An individual’s endogenous stem cell production decreases with age, this decrease likely contributes to reduced ability to regenerate and repair organs and tissues. Aging Frailty represents an exciting potential indication for cellular based therapies like Lomecel-B. This study is intended to evaluate the effects of Lomecel-B infusion compared to placebo on mobility and exercise tolerance, patient-reported physical function assessments and biomarkers for inflammation in individuals with Aging Frailty. This is a randomized, double-blind placebo-controlled, parallel multi-arm multicenter study enrolling adults aged 70-85 years identified as mildly or moderately frail per the CSHA Clinical Frailty Scale (CFS), with reduced six minute walk test (6MWT) and elevated Tumor Necrosis Factor-α (TNF-α), at screening. 150 subjects (30 per group) were randomized to receive a single peripheral intravenous infusion of 25, 50, 100, or 200 million doses, or placebo. Safety and efficacy assessments were conducted at 30, 90, 180, and 270 days after infusion. A follow up telephone call to subjects was placed at 365 days. We describe the design and rationale in detail of this 2b study assessing the effects of Lomecel-B on older adults with Aging Frailty.

Modern Approaches to Acellular Therapy in Bone and Dental Regeneration.

An approach called cell-free therapy has rapidly developed in regenerative medicine over the past decade. Understanding the molecular mechanisms and signaling pathways involved in the internal potential of tissue repair inspires the development of new strategies aimed at controlling and enhancing these processes during regeneration. The use of stem cell mobilization, or homing for regeneration based on endogenous healing mechanisms, prompted a new concept in regenerative medicine: endogenous regenerative medicine. The application of cell-free therapeutic agents leading to the recruitment/homing of endogenous stem cells has advantages in overcoming the limitations and risks associated with cell therapy. In this review, we discuss the potential of cell-free products such as the decellularized extracellular matrix, growth factors, extracellular vesicles and miRNAs in endogenous bone and dental regeneration.

Structural alignment guides oriented migration and differentiation of endogenous neural stem cells for neurogenesis in brain injury treatment

Radial glia (RG) cells that align in parallel in the embryonic brain are found to be able to guide the directed migration of neurons in response to brain injury. Therefore, biomaterials with aligned architectures are supposed to have positive effects on neural migration and neurogenic differentiation for brain injury repair that are rarely addressed, although they have been widely demonstrated in spinal cord and peripheral nerve system. Here, we present a highly biomimetic scaffold of aligned fibrin hydrogel (AFG) that mimics the oriented structure of RG fibers. Through a combination of histological, behavioral, imaging, and transcriptomic analyses, we demonstrated that transplanting the AFG scaffold into injured cortical brains promotes effective migration, differentiation, and maturation of endogenous neural stem cells, resulting in neurological functional recovery. Therefore, this study will light up a new perspective on applying an aligned scaffold to promote cortical regeneration after injury by inducing endogenous neurogenesis.

Recent advances in stem cell therapy for Parkinson’s Disease: A Review

Parkinson's disease (PD) is a degenerative neurological condition characterized by tremor, bradykinesia, and stiffness as cardinal motor characteristics. It's linked to a long-term loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc), resulting in a severe DA shortage in the striatum, which is necessary for motor function. There is presently no cure for Parkinson's disease, and the majority of treatments aimed at reversing dopamine depletion and alleviating symptoms. The transplantation of stem cells or stem cell derived progenitors has highlighted the potential of employing cell-based therapy to replace lost cells in the sick brain, based on promising findings from early experiments. Embryonic stem cells (ESCs) are highly expandable and pluripotent cells that can differentiate into any cell type in the human body, including nervous system tissues, suggesting that they could provide a long-term treatment for Parkinson's disease and other neurological illnesses. However, because of the potential for safety and ethical difficulties involved with the use of undifferentiated ESCs in people, other sources of transplantable cells must be considered. Another method is to use external manipulation to stimulate endogenous stem cells to heal the brain. Recent advances in stem cell research in Parkinson's disease will be discussed in this review, which will provide an overview of the various sources and strategies such as the use of different stem cell populations for cell replacement and possible modulation of endogenous stem cells, that have the potential to provide effective cell-based therapy in the future.

Highly Structured 3D Electrospun Conical Scaffold: A Tool for Dental Pulp Regeneration.

New procedures envisioned for dental pulp regeneration after pulpectomy include cell homing strategy. It involves host endogenous stem cell recruitment and activation. To meet this cell-free approach, we need to design a relevant scaffold to support cell migration from tissues surrounding the dental root canal. A composite membrane made of electrospun poly(lactic acid) nanofibers and electrosprayed polycaprolactone with tannic acid (TA) microparticles which mimics the architecture of the extracellular matrix was first fabricated. After rolling the membrane in the form of a 3D conical scaffold and subsequently coating it with gelatin, it can be directly inserted into the root canal. The porous morphology of the construct was characterized by SEM at different length scales. It was shown that TA was released from the 3D conical scaffold after 2 days in PBS at 37 °C. Biocompatibility studies were first assessed by seeding human dental pulp stem cells (DPSCs) on planar membranes coated or not coated with gelatin to compare the surfaces. After 24 h, the results highlighted that the gelatin-coating increased the membrane biocompatibility and cell viability. Similar DPSC morphology and proliferation on both membrane surfaces were observed. The culture of DPSCs on conical scaffolds showed cell colonization in the whole cone volume, proving that the architecture of the conical scaffold was suitable for cell migration.

Schwann cell-derived EVs facilitate dental pulp regeneration through endogenous stem cell recruitment via SDF-1/CXCR4 axis

The dental pulp is critical for physiological vitality of the tooth, and dental pulp regeneration has great potential for rebuilding live pulp tissue after pulp disease. Schwann cells (SCs) play a critical role in the support, maintenance, and regeneration of nerve fibers in dental pulp. Extracellular vesicles (EVs), which possess cell homing and tissue repair potential, derived from SCs (SC-EVs), can regulate dental mesenchymal stem cells (MSCs) proliferation, multipotency, and self-renewal. However, the role of SC-EVs in dental pulp tissue regeneration remains unclear. To address this question, we treated dental pulp stem cells (DPSCs) and bone marrow stem cells (BMSCs) with SC-EVs, and the results showed an obvious increase in the proliferation, migration, and osteogenic differentiation of both cell types. SC-EVs also promoted neurite outgrowth and neuron migration of rat dorsal root ganglia, as well as vessel formation in vitro. In an in vivo model of subcutaneous, SC-EVs enhanced the recruitment of endogenous vascular endothelioid-like cells and MSCs, and promoted the formation of a pulpo-dentinal complex-like structure. Finally, mass spectrometry analyses and western blot revealed that stromal cell-derived factor 1 (SDF-1, also known as CXCL12) plays a dominant role in SC-EVs. Together, these data suggest that SC-EVs successfully recruit endogenous stem cells to promote dental pulp regeneration. Our results provide a cell-free strategy for pulp regeneration that avoids the risks associated with stem cell transplantation. Statement of SignificanceDental pulp is vulnerable to infections resulting from dental care, trauma, and multiple restorations, with such infections resulting in pulpitis and pulp necrosis. The current endodontic treatment of irreversible pulp disease cannot restore the function of dental pulp and tissue engineering strategies using cell-based approaches are limited by several disadvantages, including immune rejection and limited cell sources. In this study, we found that schwann cells-derived EVs facilitated dental pulp regeneration through endogenous stem cells recruitment via SDF-1/CXCR4 axis without exogenous cell transplantation. We believe that our study makes a significant contribution to describe a cell-free strategy to promote dental pulp regeneration.

Application of antibody-conjugated small intestine submucosa to capture urine-derived stem cells for bladder repair in a rabbit model

The need for bladder reconstruction and side effects of cystoplasty have spawned the demand for the development of alternative material substitutes. Biomaterials such as submucosa of small intestine (SIS) have been widely used as patches for bladder repair, but the outcomes are not fully satisfactory. To capture stem cells in situ has been considered as a promising strategy to speed up the process of re-cellularization and functionalization. In this study, we have developed an anti-CD29 antibody-conjugated SIS scaffold (AC-SIS) which is capable of specifically capturing urine-derived stem cells (USCs) in situ for tissue repair and regeneration. The scaffold has exhibited effective capture capacity and sound biocompatibility. In vivo experiment proved that the AC-SIS scaffold could promote rapid endothelium healing and smooth muscle regeneration. The endogenous stem cell capturing scaffolds has thereby provided a new revenue for developing effective and safer bladder patches.

Epigenetic regulation of dental pulp stem cells and its potential in regenerative endodontics.

Regenerative endodontics (RE) therapy means physiologically replacing damaged pulp tissue and regaining functional dentin–pulp complex. Current clinical RE procedures recruit endogenous stem cells from the apical papilla, periodontal tissue, bone marrow and peripheral blood, with or without application of scaffolds and growth factors in the root canal space, resulting in cementum-like and bone-like tissue formation. Without the involvement of dental pulp stem cells (DPSCs), it is unlikely that functional pulp regeneration can be achieved, even though acceptable repair can be acquired. DPSCs, due to their specific odontogenic potential, high proliferation, neurovascular property, and easy accessibility, are considered as the most eligible cell source for dentin–pulp regeneration. The regenerative potential of DPSCs has been demonstrated by recent clinical progress. DPSC transplantation following pulpectomy has successfully reconstructed neurovascularized pulp that simulates the physiological structure of natural pulp. The self-renewal, proliferation, and odontogenic differentiation of DPSCs are under the control of a cascade of transcription factors. Over recent decades, epigenetic modulations implicating histone modifications, DNA methylation, and noncoding (nc)RNAs have manifested as a new layer of gene regulation. These modulations exhibit a profound effect on the cellular activities of DPSCs. In this review, we offer an overview about epigenetic regulation of the fate of DPSCs; in particular, on the proliferation, odontogenic differentiation, angiogenesis, and neurogenesis. We emphasize recent discoveries of epigenetic molecules that can alter DPSC status and promote pulp regeneration through manipulation over epigenetic profiles.

An improved osseointegration of metal implants by pitavastatin loaded multilayer films with osteogenic and angiogenic properties

An increasing number of works have highlighted the importance of metal implants surface modification in enhancing bone defect healing through the synergistic osteogenesis-angiogenesis regulation. Studies have shown that pitavastatin has the effect of promoting osteogenesis and angiogenesis. However, how to prepare pitavastatin functionalized implants and how pitavastatin regulates the synergies of osteogenesis and angiogenesis around implants as well as the related mechanisms remain unclear. In the present study, multilayer films with osteogenic and angiogenic properties were constructed on pure titanium substrates via the layer-by-layer assembly of pitavastatin-loaded β-cyclodextrin grafted chitosan and gelatin. In vitro experiments demonstrated that locally applied pitavastatin could dramatically enhance osteogenic potential of mesenchymal stem cells (MSCs) and angiogenic potential of endothelial cells (ECs). Moreover, pitavastatin loaded multilayer films could regulate the paracrine signaling mediated crosstalk between MSCs and ECs, and indirectly increase the angiogenic potential of MSCs and osteogenic potential of ECs via multiple paracrine signaling. The results of subcutaneous and femur implantation confirmed that locally released pitavastatin had potentially triggered a chain of biological events: mobilizing endogenous stem cells and ECs to the implant-bone interface, in turn facilitating coupled osteogenesis and angiogenesis, and eventually enhancing peri-implant osseointegration. This study enlarges the application scope of pitavastatin and provides an optional choice for developing a multifunctional bioactive coating on the surfaces of mental implants.

Programmable Building of Radially Gradient Nanofibrous Patches Enables Deployment, Bursting Bearing Capability, and Stem Cell Recruitment

AbstractFibrous patches capable of withstanding bursting force and recruiting endogenous stem cells are of great demand for wound treatment. A programmable strategy for development of radially gradient nanofibrous patches with rapid deployment property, robust bursting bearing capability, and excellent mesenchymal stem cell (MSC) recruitment capability, is demonstrated. Benefiting from the royal water lily‐like radially branched architecture, the gradient fibrous (GF) patches exhibit fast deployment in aqueous solution (2 s), high bursting strength of 4.6 N, as well as “center‐to‐periphery” gradient immobilization of stromal‐cell‐derived factor 1α (SDF1α). The SDF1α gradient patches direct MSC migration from the periphery to the center along the aligned nanofibers, resulting in a 4.2 times higher migrated cell number and 2.6 times greater maximum migration distance than random fibrous patches with homogenous SDF1α. The gelatin methacryloyl coated GF patches respond to matrix metalloproteinase‐9 for “on‐demand” release of anti‐inflammatory drug diclofenac sodium (DS). Furthermore, repair of the mouse full‐thickness skin incision validates that SDF1α/DS/GF patches are able to provide feasible microenvironment to attenuate inflammation and improve endogenous MSC recruitment, leading to accelerated wound healing. This work may open a new pathway for development of smart tough fibrous patches for stimulating endogenous repair mechanisms during tissue regeneration.

Identification of key genes involved in recovery from spinal cord injury in adult zebrafish.

Zebrafish are an effective vertebrate model to study the mechanisms underlying recovery after spinal cord injury. The subacute phase after spinal cord injury is critical to the recovery of neurological function, which involves tissue bridging and axon regeneration. In this study, we found that zebrafish spontaneously recovered 44% of their swimming ability within the subacute phase (2 weeks) after spinal cord injury. During this period, we identified 7762 differentially expressed genes in spinal cord tissue: 2950 were up-regulated and 4812 were down-regulated. These differentially expressed genes were primarily concentrated in the biological processes of the respiratory chain, axon regeneration, and cell-component morphogenesis. The genes were also mostly involved in the regulation of metabolic pathways, the cell cycle, and gene-regulation pathways. We verified the gene expression of two differentially expressed genes, clasp2 up-regulation and h1m down-regulation, in zebrafish spinal cord tissue in vitro. Pathway enrichment analysis revealed that up-regulated clasp2 functions similarly to microtubule-associated protein, which is responsible for axon extension regulated by microtubules. Down-regulated h1m controls endogenous stem cell differentiation after spinal cord injury. This study provides new candidate genes, clasp2 and h1m, as potential therapeutic intervention targets for spinal cord injury repair by neuroregeneration. All experimental procedures and protocols were approved by the Animal Ethics Committee of Tianjin Institute of Medical & Pharmaceutical Sciences (approval No. IMPS-EAEP-Q-2019-02) on September 24, 2019.

CD271 antibody-functionalized microspheres capable of selective recruitment of reparative endogenous stem cells for in situ bone regeneration

In the strategy of in situ bone regeneration, it used to be difficult to specifically recruit bone marrow mesenchymal stem cells (BM-MSCs) by a single marker. Recently, CD271 has been considered to be one of the most specific markers to isolate BM-MSCs; however, the effectiveness of CD271 antibodies in recruiting BM-MSCs has not been explored yet. In this study, we developed novel CD271 antibody-functionalized chitosan (CS) microspheres with the aid of polydopamine (PDA) coating to recruit endogenous BM-MSCs for in situ bone regeneration. The CS microspheres were sequentially modified with PDA and CD271 antibody through dopamine self-polymerization and bioconjugation, respectively. In vitro studies showed that the CD271 antibody-functionalized microspheres selectively captured significantly more BM-MSCs from a fluorescently labeled heterotypic cell population than non-functionalized controls. In addition, the PDA coating was critical for supporting stable adhesion and proliferation of the captured BM-MSCs. Effective early recruitment of CD271+ stem cells by the functionalized microspheres at bone defect site of SD rat was observed by the CD271/DAPI immunofluorescence staining, which led to significantly enhanced new bone formation in rat femoral condyle defect over long term. Together, findings from this study have demonstrated, for the first time, that the CD271 antibody-functionalized CS microspheres are promising for in situ bone regeneration.

Stem Cell‐Recruiting Injectable Microgels for Repairing Osteoarthritis (Adv. Funct. Mater. 48/2021)

Injectable Microgels Inspired by the phenomenon where islands could recruit seabirds for nesting, in article number 2105084, Xiaoji Luo, Wenguo Cui, Wei Huang, and co-workers present an injectable porous microgel generated via microfluidic technology that is non-covalently loaded with PDGF-BB and TGF-β3, forming “cell island” microgels that can serve as a temporary “nest site” to recruit endogenous stem cells and presents a promising therapeutic effect for osteoarthritic cartilage damage.